# CARTILAGE EXPRESSION AND REGULATION

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 1991 · $125,387

## Abstract

The hypothesis to be tested in these studies is that all
chondrocytes are derived from a common progenitor cell which
undergoes variations in patterns of gene expression during
cartilage development.  The objective of these studies will be to
define at a molecular level both the variations and the similarities
between chondrocytes that ultimately have different
developmental fates.  Avian chondrocytes isolated from either
caudal sterna which remains as hyaline cartilage in vivo, or
ventral vertebra which undergoes bone replacement in vivo will be
grown in vitro.  Four parameters central to the development of
these cells will be examined to explain the phenotypic variations
between these two types of chondrocytes:  a) Collagen gene
expression (types I and II) and its regulation; b) Cartilage-specific
collagen synthesis and mRNA levels (for collagen types II, IX, and
X) in chondrocytes under different experimental condition; c)
Ability of these cells to respond to specific vitamin D metabolites
(1,25 (OH)2 versus 24,25 (OH)2 and express a calcified matrix in
vitro; d) Cytoskeletal variations (actin and fibronectin expression)
between these cell types.  Previous data demonstrate that while
both chondrocyte types express high levels of collagen pro alpha
1(II) mRNAs and protein only vertebral chondrocytes express pro
alpha 1(I) and pro alpha 2(I) mRNAs.  These mRNAs, however, are
not translated into protein.  An analysis of type I collagen
transcription rates and mRNA stability will be undertaken to
determine at what level mRNA quantities are regulated in these
cells.  Type II collagen and gamma-actin transcription rates and
their stability will be similarly examined and compared as tissue-
specific and nontissue-specific genes which are expressed in
chondrocytes.  The in vivo level of translational regulation will be
defined (i.e., initiation versus elongation).  Cell lysates will be
made in other to identify whether specific factors exist that
regulate type I collagen translation in chondrocytes.  A
quantitative comparison of the protein synthesis and steady state
mRNA levels for collagen types I, II, IX and X will be undertaken
in either sternal cell, vertebral cells or in sternal cells treated
with 1,25(OH)2D3.  In conjunction with these experiments, the
effect of in vitro calcification of chondrocyte cultures on the
collagen phenotype, collagen synthesis and processing, and the
expression of bone specific proteins will be undertaken.  The final
aspect of these studies is directed at determining the functional
significance of the observed modulation of chondrocyte
morphology that has been shown to be related to the ability of
chondrocytes to express their differentiated phenotype.

## Key facts

- **NIH application ID:** 3159454
- **Project number:** 5R01AR039405-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **SAM.gov UEI:** Z1L9F1MM1RY3
- **Principal Investigator:** Louis Charles Gerstenfeld
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $125,387
- **Award type:** 5
- **Project period:** 1988-07-01 → 1992-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159454

## Citation

> US National Institutes of Health, RePORTER application 3159454, CARTILAGE EXPRESSION AND REGULATION (5R01AR039405-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159454. Licensed CC0.

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